This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HIV-1 protease (HIV PR) is an aspartic protease that is essential for the life-cycle of HIV. HIV PR cleaves newly synthesized polyproteins at the appropriate places to create the mature protein components of an infectious HIV virion. Without effective HIV PR, HIV virions remain uninfectious. Thus, mutation of HIV PR's active site or inhibition of its activity disrupts HIV's ability to replicate and infect additional cells, making HIV PR inhibition the subject of much pharmaceutical research. High Field ESR studies were undertaken of HIV PR in order to better resolve flap dynamics of the PR in inhibited and non-inhibited forms, using a variety of popular spin labels. Of the spin labels tried, MSL showed resolvable differences in the flap dynamics of inhibited and non-inhibited forms of HIV PR at 240 GHz. At lower frequencies, none of the spin labels allowed resolution of a difference in flap dynamics. Given that the 240 GHz results using MSL allow one to resolve details of the flap dynamics, and thus act as a 'fingerprint'for effective HIV PR inhibition or non-inhibition, further studies on drug-resistant strains and different inhibitors at 240 GHz are planned.